Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus
Autor(es): Pal Pankaj, Dowd Kimberly A, Brien James D, Edeling Melissa A, Gorlatov Sergey, Johnson Syd, Lee Iris, Akahata Wataru, Nabel Gary J, Richter Mareike K S, Smit Jolanda M, Fremont Daved H, Pierson Theodore C, Heise Mark T, Diamond Michael S
Resumo: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit infection of all three CHIKV genotypes. Four of 36 neutralizing MAbs (CHK-102, CHK-152, CHK-166, - CHK-263) provided complete protection against lethality as prophylaxis in highly susceptible immunocompromised mice lacking the type I IFN receptor (Ifnar(-/-) ) - mapped to distinct epitopes on the E1 - E2 structural proteins. CHK-152, the most protective MAb, was humanized, shown to block viral fusion, - require Fc effector function for optimal activity in vivo. In post-exposure therapeutic trials, administration of a single dose of a combination of two neutralizing MAbs (CHK-102+CHK-152 or CHK-166+CHK-152) limited the development of resistance - protected immunocompromised mice against disease when given 24 to 36 hours before CHIKV-induced death. Selected pairs of highly neutralizing MAbs may be a promising treatment option for CHIKV in humans.
Imprenta: PLoS Pathogens, v. 9, n. 4, p. e1003312, 2013
Identificador do objeto digital: 10.1371/journal.ppat.1003312
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2013
